This proposal builds upon the accomplishments made during the previous funding period and requests continuing support of COBRE, the Center of Biomedical Research Excellence in the Molecular Basis of Human Disease. During the four year period this COBRE grant has been active, 22 junior faculty from 9 different departments were mentored of which 8 received NIH R01 funding and an additional 4 received Other forms of extramural funding. Participating in the activities of the Center has been an additional 11 faculty, 11 postodctorals/research associates and 9 graduate students. The members of the Center published more than 175 research papers, and made 38 presentations at scientific meetings. The Department of Molecular and Cellular Biochemistry, in which the COBRE is housed, rose from 28th to 12th in NIH rankings in terms of Public Medical Schools, and 26th in terms of all Medical Schools during the tenure of the COBRE. This was accomplished by an increase in $5,148,302 of NIH grant dollars excluding the COBRE funds. The Center for Molecular Medicine was formed in 2007 as a direct consequence of the accomplishments made during the first phase of the COBRE (Aug 2004- July 2009). In the second phase of this COBRE we propose to establish a nationally and internationally recognized research center that will continue to compete effectively for extramural research funding. To accomplish this we propose i) to expand our critical mass of investigators including the mentoring of an additional 5 promising junior investigators who are studying the molecular basis of human disease. This will include a targeted new recruit to the University. We will enhance the opportunity to translate their research to patients by facilitating interactions with clinical faculty. We will continue with the major focus in cancer, diabetes, and neurological diseases, ii) We will expand and continue to develop our core facilities in Proteomics, Chemistry, Microscopy, Protein characterization, and Mouse Genotyping. iii) We will continue to support pilot research projects. This has been a highly effective way to enhance the research of a rather significant number of junior faculty; iv) facilitate the development of a sustainable center through the submission of program project grants and multi-PI grants. We will provide staff resource and pilot funding to enhance these activities.